The activation of B cells is a complex process which is still poorly understood. The overall objective of this research is to evaluate the roles of the interactions of helper-T cells with Ia antigens on the B-cell membrane and surface immunoglobulin with specific antigen in: (1) the activation of resting B cells; (2) the replication of B cells; and (3) their maturation to immunoglobulin synthesis. The activation of resting unprimed and antigen-primed "memory" B cells will be compared to determine what differences, if any, exist in their properties. We will also initiate studies to evaluate the repertoire of immunoglobulin genes in B-cell responses to the autoantigen, senescent autologous erythrocytes. The idiotypic profile of this response if controlled, at least in part, by major histocompatibility complex-encoded immune response genes. These studies will be facilitated by the virtual exclusive use of purified populations of resting and activated sntigen-binding B cells and clones of antigen-specific B cells, including a B-cell lymphoma which has the activation properties of a resting B cell. As helper T cells, lines and clones of sntigen-specific helper cells will be used, and as sources of nonspecific factors, supernatants from antigen-speclfic T-cell lines and functionally defined T-cell lymphomas will be utilized. These studies will provide information necessary for our understanding of the basis of specificity of the immune response and the regulation of functional interactions of lymphocyte subpopulations. Moreover, they will provide us with initial information on the similarities and differences between the diveraity of the B-cell response to endogenous and exogenous antigens. (LB)